Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of ATP, ADP, AMP, NADP, NADPH, NAD, NADH and reduced glutathione were determined in the red blood cells of individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, beta-thalassemia (beta-thal) heterozygotes and in a boy carrying both mutations. The results obtained confirmed a reduced concentration of NADPH in G6PD deficiency and showed that with the combination of both diseases, the red blood cell contained practically undetectable levels of NADPH. Assays of some red blood cell enzyme activities known to be markedly influenced by cell age suggested that a younger mean red cell population is present in beta-thal/G6PD deficiency. Thus, the marked oxidative stress caused by beta-thal, that is apparently incompatible with G6PD deficiency, in fact exists, probably because of the residual activity of this enzyme in the younger red cells.
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PMID:Redox and energetic state of red blood cells in G6PD deficiency, heterozygous beta-thalassemia and the combination of both. 309 52

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.
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PMID:Interaction of antioxidants and their implication in genetic anemia. 1060 86

A common perturbation found in cells under oxidative stress is alteration in cellular Ca2+ homeostasis. In order to understand the effects of such oxidative damage, human red cell plasma membrane Ca(2+)-ATPase (PMCA) was studied by measuring PMCA activity, both in the presence and absence of calmodulin (CaM), following treatment with sulfhydryl agents, N-ethylmaleimide, iodoacetate and diamide. PMCA activity of washed red cell membrane was measured by coupling with pyruvate kinase, using phosphoenolpyruvate as substrate, and lactate dehydrogenase to convert pyruvate to lactate employing beta-NADH as co-factor. All treatments inhibited basal and CaM-stimulated activity in a dose-dependent manner (0.01-1 mM), but at low concentrations, basal Ca(2+)-ATPase activity was inhibited whereas CaM-stimulated activity was unaffected. Inhibition by diamide, a disulfide-forming agent, was reversed with dithiotreitol (DTT). Treatment with calpain, a calcium-dependent protease, elevated basal PMCA activity to CaM-stimulated level, but abolished response to CaM. Further treatment with diamide inhibited PMCA activity, which could be restored by DTT, but only to basal and not CaM-stimulated level. These studies indicated that it is necessary to protect against both sulfhydryl and proteolytic damages to red cell PMCA if perturbation to Ca2+ homeostasis is to be minimized. This has implications for membranes under oxidative stress, such as in the hereditary anemia, thalassemia, where membrane-bound unmatched hemoglobin chains cause oxidative damage to red blood cells.
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PMID:Plasma membrane Ca(2+)-ATPase sulfhydryl modifications: implication for oxidized red cell. 2343 34

Pathogenesis of different diseases showed that some of them, especially thalassemia (T) and rheumatoid arthritis (RA) have an implicit association with oxidative stress and altered levels of reactive oxygen species (ROS). Introducing ROS level and the balance between ROS and antioxidants as essential metrics, an attempt was made to classify T and RA from normal individuals (treated as controls)(C) using synchronous fluorescence spectroscopy (SFS) and Raman line intensity of water. This non-invasive and label-free approach was backed up by a categorization algorithm that helped in the prediction of disease types from serum samples. The predictive system constituted principal component analysis (PCA) with four parameters, namely spectral intensity ratios of reduced nicotinamide adenine dinucleotide (NADH) to tryptophan (Trp) (NADH/Trp), kynurenine (Kyn) to tryptophan (Kyn/Trp), kynurenine to NADH (Kyn/NADH), and logarithmic changes in Raman line intensity of water (Rline), with the index headers containing the disease types. Rline has a positive correlation with both Kyn/Trp and Kyn/NADH and a negative correlation with NADH/Trp ratio, implying its direct or indirect association with oxidative stress. In addition to the classification of T, RA, and C a sub-classification of T into beta major and E-beta in their post and pre-splenectomized surgical stages could also be realized. Furthermore, receiver operating characteristic (ROC) analysis was deployed to ascertain that the misclassification error (ME) was negligible for the disease types. Graphical Abstract A schematic representation of the workflow converging into the categorical classification of disease classes.
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PMID:Label-free detection of thalassemia and other ROS impairing diseases. 3268 Dec 15